A65-07 Inhaled Prostacyclin Improves Clinical and Hemodynamic Parameters in Sarcoidosis Patients With Pulmonary Hypertension and Interstitial Lung Disease (SAPPHIRE Trial)

Rationale Sarcoidosis is a multisystem inflammatory disease with complex pulmonary parenchymal and vascular involvement. Pulmonary hypertension associated with sarcoidosis-related interstitial lung disease (S-ILD-PH) represents the most common cause of PH in this population and portends a poor prognosis. Current management primarily targets immunosuppression, while pulmonary vasodilator therapy is often limited by risks of hypoxemia and pulmonary edema. Although pivotal trials recommend inhaled prostacyclin for PH due to interstitial lung disease, data specifically addressing its use in S-ILD-PH are scarce. We hypothesized that inhaled prostacyclin improves hemodynamic and clinical outcomes in patients with S-ILD-PH. Methods In this single-center, open-label, prospective study, we enrolled patients with biopsy-confirmed pulmonary sarcoidosis and newly diagnosed pulmonary hypertension, defined as mean pulmonary artery pressure (mPAP)>20 mmHg, pulmonary capillary wedge pressure (PCWP) ≤15 mmHg, and pulmonary vascular resistance (PVR) ≥2 Wood units. Patients with FEV1 <30%, left heart disease, or pregnancy/lactation were excluded. Inhaled prostacyclin was titrated to a target dose of 12 breaths (72 μg) four times daily by week 4. Clinical assessments, laboratory testing, pulmonary function testing, right heart catheterization, and cardiac MRI were performed at baseline and week 16. Results The study was terminated early due to low enrollment. Four patients (three female; mean age 59.5 years) completed the study and one patient was lost to follow up. Baseline oxygen requirement was 2 L/min with exertion. The average tolerated maintenance dose achieved was 10 puffs four times daily. At 16 weeks, all patients experienced an increase in WHO functional class, reflected by improvement in dyspnea and perceived exercise tolerance, without worsening hypoxia. Across the cohort, mean PVR improved from 4.6 to 3.5 WU (p < 0.0046) with mild reduction in mPAP and RA pressure and stable cardiac output, although not statistically significant. Additionally, there was a mild reduction in RV mass and RVEDV with RVEF increased by 3.9%. Spirometry parameters and 6MWT distance remained stable. Cough was the most frequent side effect but did not lead to drug discontinuation. All participants elected to continue therapy after study completion. Conclusions In patients with sarcoidosis associated ILD-PH, inhaled prostacyclin improved clinical, hemodynamic, and cMRI parameters with minimal adverse effects. While limited by sample size, these preliminary findings suggest inhaled prostacyclin may represent a safe and effective therapeutic option in this challenging population and warrant confirmation in larger, controlled studies. This abstract is funded by: Jenesis Innovative Research Award